Protoescigenin is one of the aglycons contained in saponin mixture known as “escin” which is derived from Aesculus family (Pharmaceutical Crops, 2010, 1, 24-51). Saponins are classified as triterpene polyhydroxyl glycosides based on four different aglycons (sapogenins) including escigenin, protoescigenin, barringtogenol C and barringtogenol D, differing by substituents at C16/C21 and C24 positions. Up to now, 79 saponines have been isolated from hydrolysates of saponine mixtures.
The composition of saponins mixtures obtained from Aesculus family varies and depends on the species and origin of the plant material. Chemical composition of the saponins mixture derived from horse chestnut seeds (Aesculus hippocastanum L.) of the tree growing mainly in Europe and North America, suggested by R. Tschesche in Liebig's Ann. 669, 171 (1963) can be depicted by following formula based on Pharmaceutical Crops., 2010, 1, 24-51:

Horse chestnut extracts have been recognized by ethnopharmacological tradition as a remedy for fever, oedema and hemorrhoidal conditions. Clinical trials confirm that it may be also used in case of chronic venous insufficiency and capillary vessel fragility (EMEA Committee on Herbal Medicinal Products, Assessment Report on Aesculus hippocastanum L., semen, EMEA/HMPC/225304/2008, 1 (2009)).
β-Escin is also used as an active ingredient of numerous pharmaceutical preparations which are available on the market. However, from the medical chemistry point of view, β-escin being a complex mixture of many structurally related substances is not a promising material for development of modern medicine. Furthermore, despite the advances in modern analytic and preparatory techniques, it is very difficult to isolate individual components of escin. Thus, the only realistic way to obtain and examine individual mimetics of the natural escin complex mixture is to conduct chemical synthesis and analysis of such newly designed analogs.
WO2005/051969 discloses various compounds obtained from plants of the Barringtonia species which are derived from barringtoside A and barringtoside C as precursor compounds which especially have an arabinopyranosyl substituent at the 21 position which may optionally be further substituted with benzoyl, dibenzoyl, methyl butanoyl, methyl butyryl or tigloyl at the 3 or 4 positions. Alternatively at the 21 position there is tigloyl, benzoyl or dibenzoyl substituents. Said compounds exhibit analgesic properties.
WO2006/116656 describes compositions comprising a triterpenoidal saponin, triterpenoid, triterpenoidal compound or sapongenin, comprising at least two side groups selected from the group consisting of angeloyl groups, tigloyl groups and senecioyl groups, wherein the side groups are attached to carbon 21, 22 or/and 28 of triterpenoidal sapogenin, triterpenoid, triterpenoidal compound or other sapongenin backbones. These compositions are useful for inhibiting tumor cell growth, treating varicose vein disease, venous insufficiency, particularly hemorrhoids or leg swelling.
WO2008/028060 discloses pharmaceutical compositions comprising triterpenoid saponin, triterpenoid, triterpenoid compound or sapongenin, comprising at least two side groups selected from the group consisting of angeloyl groups, tigloyl groups and senecioyl groups, wherein the side groups are attached to carbon 21, 22 or/and 28 of triterpenoid sapogenin, triterpenoid, triterpenoid compound or other sapongenin backbones. These compositions are useful for treating cancer by blocking the migration, metastasis of cancer cells and growth of cancers.
There is still a need for new compounds which are structurally related to the components of saponin mixture, which would have analogous activity but have well defined structure and which would be useful as active agents for modern medicines.
The present invention provides such compounds. The inventors surprisingly found that the newly synthesized protoescigenin derivative exhibits advantageous properties and may be useful as pharmaceutical.